Abstract
Two chemically related arylazido photoaffinity analogs of ATP (arylazido aminopropionyl ATP (ANAPP 3) and arylazido aminobutyryl ATP (ANABP 3)), which have been reported in the literature to differ in their ability to inhibit myosin ATPase, were compared for their ability to antagonize contractile responses of the isolated guinea-pig vas deferens to ATP. During photolysis in organ chambers the photoconversion (ΔA 260/Δt) of ANAPP 3 occured with greater than first order kinetics or was multiexponential and t 1 2 = 7.5 min , while ΔA 260/Δt for ANABP 3 was first order and t 1 2 = 2.25 min . After photolysis of these compounds in the presence of the guinea-pig vas deferens, using irradiation periods which caused 80% consumption of the compounds, ANABP 3 was 2–3 times more potent than ANAPP 3 in antagonizing contractions to ATP, which are mediated by P 2-purinergic receptors. A comparison of concentration-response curves obtained for nonphotolyzed ANAPP 3 and ANABP 3 used as agonists suggested that the greater antagonism produced by photolyzed ANABP 3 is not attributable to a greater potency. The results suggest that the longer 3′-hydroxyl-arylazide bridge length of ANABP 3 places the arylnitrene intermediate in a position at or near the P 2-receptor which is more favorable for covalent insertion.
Published Version
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